No pain for Actavis - Warner-Lambert fail to stop launch of generic pregabalin
In a decision that is only moderately Arnoldian (139 paragraphs), Mr Justice Arnold refused today to grant an interim injunction that Warner Lambert had requested against Actavis [Warner -Lambert Company, LLC v Actavis Group Ptc EHF & Others [2015] EWHC 72 (Pat) (21 January 2015)]. The case is a tricky one, exploring second medical use claims, skinny labels, and public policy issues around healthcare. The background is also quite complex, so this moggy will try to explain.
Background
Warner-Lambert (part of the Pfizer group) had a patent for pregabalin, which it markets for epilepsy, generalised anxiety disorder ("GAD") and neuropathic pain under the trade mark Lyrica. The original product patent has expired, and, for reasons which are intriguing but not disclosed, Warner-Lambert obtained a supplementary protection certificate which extended protection for pregabalin to 17 May 2018, but allowed it to lapse for non-payment of fees (this Kat would love to know why). Data exclusivity expired in July 2014, so in principle generic companies are now free to launch a competitive product.
The patent
Except that Warner Lambert has a second medical use patent - European Patent (UK) No. 0 934 061 - relating to the third indication, which has claims as follows:
In principle there is a well established procedure in such circumstances - the generic company can launch a product with a "skinny label" - an edited product leaflet that mentions only the permitted indications. But when one considers how things work in reality, immediately it is clear that there are problems. Prescriptions do not mention the indication for which a drug is prescribed. So in any situation, it is not clear to the pharmacist the reason for a drug prescription, let alone to the generic manufacturer for what indications a pharmacist may dispense a drug supplied to them.
The relief sought
So the interim injunction that Warner-Lambert were seeking was one of Actavis taking very special and particular steps to ensure that product that they supplied was not in the end dispensed for use in the patented indication. Thus the order that Warner-Lambert sought against the Defendant Actavis in relation to their pregabalin product Lecaent was:
The decision
In relation to the letters in 3) and 6) Actavis basically agreed anyway to write to pharmacies and Clinical Commissioning Groups to inform them that Lecaent should not be used for pain, although there was some quibbling over the precise wording.
In relation to 5), NICE had already amended its Clinical Guideline 73 "Neuropathic pain – pharmaceutical management" with a footnote:
In relation to 4), it was not clear that such a labelling would comply with the relevant regulations for packaging of pharmaceuticals, so such an order presented difficulties.
When deciding overall whether to grant the injunction, Arnold J applied the classical principles set out in American Cyanamid, and confirmed by the Privy Council in National Commercial Bank Jamaica Ltd v Olint Corp Ltd
He determined that in relation to the main infringement action there was no serious issue to be tried: in marketing pregabalin in the manner proposed, Actavis did not infringe a Swiss-form claim as Arnold construed it. In the alternative, he also decided that in any case the balance of the risk of injustice favoured Actavis:
A Swiss form claim (Use of a compound of general formula X in the preparation of a medicament for the treatment of Y) contains a medical indication with a statement of purpose - in this case "for treating pain". On the face of it, this wording brings in the intent of the doctor and possibly the pharmacist. However, if such claims were really infringed by a doctor, it would call into question the efficacy of this claim form in overcoming the prohibition (See Section 4A of the UK Patents Act 1977) on patenting of methods of medical treatment. The rationale of this prohibition is usually understood to be to exclude doctors and the practice of medicine from the realm of patent law. Thus, as Jacob LJ explained in Actavis v Merck at [75], such a claim "is not aimed at and does not touch the doctor - it is directed at the manufacturer." In this decision, Arnold went further and confirmed that intention is important in such a claim, but it is the intention of the manufacturer that matters:
Since there is surprisingly little jurisprudence on what actually is required to infringe a Swiss claim (or the corresponding form of second medical use claim under the EPC 2000 - "A compound of general formula X for use in the treatment of Y"), this part of the judgment is most welcome.
Background
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| Happier times ... |
The patent
Except that Warner Lambert has a second medical use patent - European Patent (UK) No. 0 934 061 - relating to the third indication, which has claims as follows:
1. Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain.This patent would be infringed by a generic pharmaceutical company marketing pregabalin for this indication.
3. Use according to Claim 1 wherein the pain is neuropathic pain
The relief sought
So the interim injunction that Warner-Lambert were seeking was one of Actavis taking very special and particular steps to ensure that product that they supplied was not in the end dispensed for use in the patented indication. Thus the order that Warner-Lambert sought against the Defendant Actavis in relation to their pregabalin product Lecaent was:
1, The Defendants: (a) shall make it a condition of any oral or written agreement entered into with a pharmacy for the supply of Lecaent that the pharmacy shall use reasonable endeavours not to supply or dispense Lecaent to patients who have been prescribed pregabalin for the treatment of pain, by making reasonable enquiries of a person presenting a prescription for 'pregabalin' as to whether the prescription is for pain and/or making reasonable checks of pharmacy records for the same; and (b) shall make it a condition of any oral or written agreement entered into with an intermediary (such as a distributor) for the supply of Lecaent that, in any onward supply of Lecaent by the intermediary, such intermediary must in turn make it a condition of any onward supply agreement for the supply of Lecaent that the receiving pharmacy shall use reasonable endeavours as specified in (a) above.Arnold J considered that:
2. Insofar as the Defendants are to supply Lecaent to intermediaries (such as a distributor) they inform the Claimant's solicitors of the name of that intermediary prior to supply.
3. No later than the date of first supply of Lecaent to a pharmacy in the United Kingdom, the Defendants shall write a letter, in the form attached, to the superintendent pharmacist responsible for the pharmacy to which Lecaent is to be supplied.
4. Prior to launch of Lecaent in the United Kingdom the First, Second and Third Defendants and each of them shall ensure that each pack of Lecaent supplied to a pharmacist is accompanied by removable notification that is easily legible stating:
'This product is not authorised for the treatment of pain and must not be dispensed for such purposes.'
5. The Defendants shall notify in writing forthwith, and in any event before the date of first supply of Lecaent to a pharmacy in the United Kingdom, the NICE Medicines and Prescribing Centre of the Department of Health informing it that Lecaent should not be prescribed or dispensed for the treatment of pain.
6. No later than the date of first supply of Lecaent to a pharmacy in the United Kingdom, the Defendants shall write a letter, in the form attached, to all Clinical Commissioning Groups in the UK.
it is more or less common ground between all concerned that the best solution to the problem which arises in this case is to try to ensure that prescribing doctors prescribe pregabalin for the treatment of pain by reference to the brand name Lyrica rather than by reference to the generic name pregabalin. That will ensure that pharmacists only dispense Lyrica when presented with prescriptions for pregabalin which are (at least so far as the prescriber is concerned) for pain without requiring the pharmacist to know the indication for which pregabalin has been prescribed.The issue is to what lengths Actavis should be expected to go to ensure that this was what happened.
The decision
In relation to the letters in 3) and 6) Actavis basically agreed anyway to write to pharmacies and Clinical Commissioning Groups to inform them that Lecaent should not be used for pain, although there was some quibbling over the precise wording.
In relation to 5), NICE had already amended its Clinical Guideline 73 "Neuropathic pain – pharmaceutical management" with a footnote:
In addition, the Lyrica (Pfizer) brand of pregabalin has patent protection until July 2017 for its licensed indication of peripheral and central neuropathic pain; until such time as this patent expires generic pregabalin products will not be licensed for this indication and their condition would be off-label and may infringe patent.Arnold J accepted that Actavis could not force NICE to do any more than that.
In relation to 4), it was not clear that such a labelling would comply with the relevant regulations for packaging of pharmaceuticals, so such an order presented difficulties.
When deciding overall whether to grant the injunction, Arnold J applied the classical principles set out in American Cyanamid, and confirmed by the Privy Council in National Commercial Bank Jamaica Ltd v Olint Corp Ltd
He determined that in relation to the main infringement action there was no serious issue to be tried: in marketing pregabalin in the manner proposed, Actavis did not infringe a Swiss-form claim as Arnold construed it. In the alternative, he also decided that in any case the balance of the risk of injustice favoured Actavis:
In my judgment, granting the relief sought by Warner-Lambert would create a greater risk of injustice than refusing it. In my view, wrongly granting the relief is more likely to cause Actavis substantial unquantifiable harm than wrongly refusing it is likely to cause Warner-Lambert substantial unquantifiable harm.Swiss form claims
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| Making a Swiss claim? |
counsel for Warner-Lambert submitted that the relevant intention was not that of the manufacturer, but that of the person who disposes, or offers to dispose, of pregabalin. I do not accept this submission. As I have explained, the claim is to a process of manufacture and it is directed at the manufacturer. It is not a claim to the resulting pharmaceutical composition, nor is it directed at a person who disposes of the pharmaceutical composition. It follows that the relevant intention is that of the person who carries out the process, here Actavis (or their manufacturer).Moreover, it is a subjective intention that it be used for the claimed use that is required for infringement:
Accordingly, I hold that the word "for" in Swiss form claims imports a requirement of subjective intention on the part of the manufacturer that the medicament or pharmaceutical composition will be used for treating the specified condition.On this basis, there was no serious issue to be tried that Actavis's sales in the manner planned would infringe the patent.
Since there is surprisingly little jurisprudence on what actually is required to infringe a Swiss claim (or the corresponding form of second medical use claim under the EPC 2000 - "A compound of general formula X for use in the treatment of Y"), this part of the judgment is most welcome.
